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Simple Summary: The initial treatment for patients with advanced-stage follicular lymphoma is usually a combo of immunochemotherapy called R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-bendamustine (R-B, for short). After six cycles of R-CHOP, continuing with rituximab for two years (maintenance therapy) has demonstrated a reduction in relapses. However, determining if this approach works well after R-B has yet to be confirmed. Here, we collected data from 476 FL patients from 17 GELTAMO centers and evaluated the efficacy of both regimens followed by rituximab maintenance therapy in untreated follicular lymphoma patients. We found a better response with R-B and relapses were more frequent with R-CHOP. During the initial treatment, low blood counts were more frequent with R-CHOP but, during maintenance therapy, they were more frequent with R-B and so were infectious complications. After six years, 79% and 67% of R-B- and R-CHOP-treated patients, respectively, did not have evidence of the disease but the number of deaths was the same in both groups. In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated follicular lymphoma showed better responses and fewer relapses, without any extra side effects in an elderly population. During maintenance, patients had more issues when using R-B but deaths were the same in both groups. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77–86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72–86) for R-bendamustine vs. 67% (95% CI: 61–73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86–96) for R-B vs. 91% (95% CI: 87–94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: Inherited predisposition to hematological malignancies is more common than previously perceived. The main objective of our study was to analyze the whole-exome sequencing data for the genomic characterization of sixteen patients with a strong family or personal onco-hematological history. When a duo analysis was performed, we detected pathogenic or likely pathogenic (P/LP) germline variants in four out of the six families studied. In the remaining four individuals, we detected three P/LP germline variants in genes with a potential role in cancer development. Next-generation sequencing strategies lead to the identification of novel candidate genes (NFATC2 and TC2N) potentially involved in the development of these germline syndromes. The recognition of predisposing variants is crucial for disease management and follow-up of affected patients and their relatives. The familial occurrence of hematological malignancies has been underappreciated. Recent studies suggest that up to 15% of adults with myeloid neoplasms carry germline pathogenic variants in cancer-predisposing genes. This study aimed to identify the underlying germline predisposition variant in patients with a strong family or personal onco-hematological history using whole exome sequencing on sixteen uncharacterized individuals. It was carried out in two groups of patients, one with samples available from two affected relatives (Cohort A) and one with available samples from the index case (Cohort B). In Cohort A, six families were characterized. Two families shared variants in genes associated with DNA damage response and involved in cancer development (CHEK2 and RAD54L). Pathogenic or likely pathogenic germline variants were also found in novel candidate genes (NFATC2 and TC2N). In two families, any relevant pathogenic or likely pathogenic genomic variants were identified. In Cohort B, four additional index cases were analyzed. Three of them harbor clinically relevant variants in genes with a probable role in the development of inherited forms of hematological malignancies (GATA1, MSH4 and PRF1). Overall, whole exome sequencing is a useful approach to achieve a further characterization of these patients and their mutational spectra. Moreover, further investigations may help improve optimization for disease management of affected patients and their families. [ABSTRACT FROM AUTHOR]

Simple Summary: Follicular lymphoma (FL) is the most prevalent subtype of indolent lymphoma, accounting for 70% of all cases. The estimated risk of histological transformation (tFL), such as diffuse large B cell lymphoma (DLBCL), varies from 2–3% per year to 7–8% at 10 years in different series. Treatment after transformation is not clearly established. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be an option for these patients, but it has not been widely explored. We analyze the efficacy and toxicity of alloSCT in 43 patients from 14 Spanish centers. We observed long-term survival in around one third of the patients, especially those who developed chronic graft versus host disease, indicating that alloSCT continues to be a potentially curative option for patients with tFL, mainly due to the graft versus lymphoma effect. Background: Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be a potentially curative option for these patients, but it has not been widely explored. Methods: We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival. Results: A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31–67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2–9.6). Conclusions: Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL. [ABSTRACT FROM AUTHOR]

Simple Summary: Conventional cytogenetic approaches are the gold standard for the identification of chromosomal alterations in myeloid neoplasms. Next-generation sequencing panels are a new approach for the detection of copy number variations (CNV) or translocations. Here we report on a commercial panel utility including frequent mutations, CNVs and translocations in myeloid neoplasms. A total of 135 patients with myeloid neoplasms and three with acute lymphoblastic leukemia were analyzed by NGS. When comparing with gold standard techniques, 48 frequent alterations were detected by both methodologies, ten of them observed only by conventional methods and another eight only by NGS. Additionally, 38 secondary CNVs were detected in any of the genes included in the panel for mutational analysis. With those results we determine that NGS represents a reliable complementary source of information for the analysis of CNVs and translocations. Conventional cytogenetics are the gold standard for the identification of chromosomal alterations recurrent in myeloid neoplasms. Some next-generation sequencing (NGS) panels are designed for the detection of copy number variations (CNV) or translocations; however, their use is far from being widespread. Here we report on the results of a commercial panel including frequent mutations, CNVs and translocations in myeloid neoplasms. Frequent chromosomal alterations were analyzed by NGS in 135 patients with myeloid neoplasms and three with acute lymphoblastic leukemia. NGS analysis was performed using the enrichment-capture Myeloid Neoplasm-GeneSGKit (Sistemas Genómicos, Spain) gene panel including 35 genes for mutational analysis and frequent CNVs and translocations. NGS results were validated with cytogenetics and/or MLPA when possible. A total of 66 frequent alterations included in NGS panel were detected, 48 of them detected by NGS and cytogenetics. Ten of them were observed only by cytogenetics (mainly trisomy 8), and another eight only by NGS (mainly deletion of 12p). Aside from this, 38 secondary CNVs were detected in any of the genes included mainly for mutational analysis. NGS represents a reliable complementary source of information for the analysis of CNVs and translocations. Moreover, NGS could be a useful tool for the detection of alterations not observed by conventional cytogenetics. [ABSTRACT FROM AUTHOR]

Simple Summary: As the optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma (HL), with the aim to identify the best one, we analyzed surveillance strategies after first-line treatment in a group of 640 Hodgkin lymphoma patients from 15 different GELTAMO centers in Spain. In this study, we have demonstrated that surveillance approaches with imaging in HL do not provide benefits for patient survival, nor do they anticipate relapse. Our results are of great importance, because they could contribute to improve the follow up after first complete response of this group of patients. The optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma. Thus, we compared the various follow-up strategies in a multicenter study. All the included patients had a negative positron emission tomography/computed tomography at the end of induction therapy. From January 2007 to January 2018, we recruited 640 patients from 15 centers in Spain. Comparing the groups in which serial imaging were performed, the clinical/analytical follow-up group was exposed to significantly fewer imaging tests and less radiation. With a median follow-up of 127 months, progression-free survival at 60 months of the entire series was 88% and the overall survival was 97%. No significant differences in survival or progression-free survival were found among the various surveillance strategies. This study suggests that follow-up approaches with imaging in Hodgkin lymphoma provide no benefits for patient survival, and we believe that clinical/analytical surveillance for this group of patients could be the best course of action. [ABSTRACT FROM AUTHOR]

Molecular diagnosis of myeloid neoplasms (MN) is based on the detection of multiple genetic alterations using various techniques. Next-generation sequencing (NGS) has been proved as a useful method for analyzing many genes simultaneously. In this context, we analyzed diagnostic samples from 121 patients affected by MN and ten relapse samples from a subset of acute myeloid leukemia patients using two enrichment-capture NGS gene panels. Pathogenicity classification of variants was enhanced by the development and application of a custom onco-hematology score. A total of 278 pathogenic variants were detected in 84% of patients. For structural alterations, 82% of those identified by cytogenetics were detected by NGS, 25 of 31 copy number variants and three out of three translocations. The detection of variants using NGS changed the diagnosis of seven patients and the prognosis of 15 patients and enabled us to identify 44 suitable candidates for clinical trials. Regarding AML, six of the ten relapsed patients lost or gained variants, comparing with diagnostic samples. In conclusion, the use of NGS panels in MN improves genetic characterization of the disease compared with conventional methods, thus demonstrating its potential clinical utility in routine clinical testing. This approach leads to better-adjusted treatments for each patient. [ABSTRACT FROM AUTHOR]

The study aimed to assess the cost-effectiveness of axicabtagene ciloleucel (axi-cel) vs. tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 lines of systemic therapy in Spain. A lifetime partitioned survival mixture cure model, which comprises pre-progression, post-progression, and death health states, was used to estimate the accumulated costs and outcomes in terms of life years gained (LYG) and quality-adjusted life years (QALY). A matching-adjusted indirect comparison was used to reweight patient-level data from ZUMA-1, the pivotal clinical trial for axi-cel, to aggregate-level data from the pivotal tisa-cel trial, JULIET. The analysis was performed from the National Health System perspective, thus only direct costs were included. Sensitivity analyses (SA) were performed. Axi-cel yielded 2.74 incremental LYG and 2.31 additional QALY gained per patient compared to tisa-cel. Total incremental lifetime costs for axi-cel versus tisa-cel were €30,135/patient. The incremental cost-effectiveness ratio of axi-cel versus tisa-cel resulted in €10,999/LYG and the incremental cost-utility ratio in €13,049/QALY gained. SA proved robustness of the results. Considering the frequently assumed willingness-to-pay thresholds in Spain (€22,000/QALY and €60,000/QALY), axi-cel is a cost-effective treatment vs. tisa-cel for adult patients with R/R DLBCL in Spain.